A variety of radioisotope imaging and labelling agents have been developed in the past; however, the materials previously available have generally suffered from the shortcomings of high cost, complexity of the method of preparation, or failure to exhibit high quality imaging or highly effective labelling.
Isonitrile complexes of various non radioactive metals have been described but there has been no suggestion that isonitrile complexes of radionuclides would have properties making them desirable or useful as imaging or labelling agents. Oxine complexes of .sup.99m Tc have been described for use in labelling platelets. Wistow et al., J. Nucl. Med., Vol. 19, 483-487 (1978). The direct labelling of red blood cells with .sup.99m Tc by a reductive process, and the use of the labelled cells for imaging have been described. Smith et al., J. Nucl. Med., Vol. 17, -132 (1976). Various complexes of .sup.99m Tc with arsenic- and phosphorus-containing organic compounds have been proposed for use as imaging and labelling agents. Deutsch et al., Science, Vol 214, 85-86 (1981); J. Nucl. Med., Vol. 22, 897-907 (1981); European Pat. Appln. No. 81400618.5, published Oct. 28, 1981, Publn. No. 0038756.
U.S. Pat. No. 4,452,774 describes a coordination complex of an isonitrile ligand with a radioactive metal (radionuclide) selected from the class consisting of radioactive isotopes of Tc, Ru, Co, Pt, Fe, Os, Ir, W, Re, Cr, Mo, Mn, Ni, Rh, Pd, Nb, and Ta, and methods for using such complexes. Preferably, the isonitrile complexes comprise one of the above radioactive metals wherein each available coordination site is filled with an isonitrile ligand. The isonitrile ligand can be either monodentate or polydentate such as, for example, bidentate or tridentate. Also described is a kit comprising an isonitrile ligand and a reducing agent capable of reducing the radioactive metal to form the coordination complex.
Because of the general availability of supplies of .sup.99m Tc in clinical laboratories in the form of pertechnetate as well as the desirable half-life and gamma ray energy of this radionuclide, the complexes preferably contain .sup.99m Tc, although complexes with other radionuclides are also described. Moreover, the general availability of supplies of pertechnetate make it convenient to use kits for preparation of various complexes of .sup.99m Tc.
The isonitrile complexes can readily be prepared and isolated at both macro and tracer concentrations in aqueous media, together with any of a wide variety of counterions, as appropriate. They display remarkably effective labelling characteristics for liposomes or vesicles, and a variety of living cells containing lipid membranes, and are also effective imaging agents for detecting abnormalities in the tissues of various organs, particularaly in the heart, as well as the existence of blood clots. The complexes of .sup.99m Tc are particularly preferred because of the desirable nuclear properties of this radioisotope, i.e., its half-life and gamma ray energy.
One problem encountered in preparing the isonitrile complexes described in U.S. Pat. No. 4,452,774 is that many isonitrile ligands are extremely volatile. Thus, the isonitrile ligand is difficult to handle and lyophilized kits are not practical. Therefore, new and better ways for handling the isonitrile ligands for making radionuclide complexes are being sought.